Browsing by Author "Inan, S"
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Item Influence of VEGF and TNF antagonism on zonula occludens proteins in an experimental asthma modelYuksel, H; Yilmaz, O; Karaman, M; Firinci, F; Turkeli, A; Kanik, ET; Inan, SItem Immunolocalization of VEGF, VEGF receptors, EGF-R and Ki-67 in leiomyoma, cellular leiomyoma and leiomyosarcomaSanci, M; Dikis, C; Inan, S; Turkoz, E; Dicle, N; Ispahi, CAngiogenic factors, such as vascular endothelial growth factor (VEGF), its receptors and epidermal growth factor receptor (EGF-R), are involved in increased progression in many carcinomas. The aim of this study was to investigate the role of angiogenesis and immunolocalization of VEGF, its receptors, EGF-R and Ki 67 in leiomyomas and leiomyosarcomas using an indirect immunohistochemical method. Samples from patients with leiomyoma, cellular leiomyoma and cellular leiomyosarcoma (n=20 per group) were fixed in 10% formalin and processed using routine paraffin protocols. Following initial histological analysis, samples were immunostained with primary antibodies for VEGF, VEGFR-1, VEGFR-2, EGF-R and Ki-67 using an indirect avidin-biotin peroxidase method. Immunostaining intensities were evaluated as mild, moderate or strong and a semi-quantitative method (H-Score) was used to compare the samples. While mild/moderate EGF-R immunostaining and moderate immunostaining for VEGF and its receptors were observed in samples of leiomyomas, much less immunoreactivity was observed in cellular leiomyomas. All immunoreactivities and immune-stained cells increased in leiomyosarcomas. When scores of intensity and percentage of positive staining cells were compared, all immunoreactivities were shown to be significantly increased in leiomyosarcomas compared to leiomyomas. These results suggest that in leiomyosarcoma, angiogenic factors, such as VEGF, its receptors and EGF-R, may be involved in tumor angiogenesis. Active tumor cells can trigger angiogenesis, interaction with surrounding tissue and in the tissue itself initiating angiogenic activity. Angiogenic growth factors play an important role and induce malignant transformation through both autocrine and paracrine mechanisms. Anti-angiogenic agents may provide a novel therapeutic approach for the treatment of leiomyosarcoma. (C) 2010 Elsevier GmbH. All rights reserved.Item Netherton's Syndrome: An Ultrastructural Study: Case ReportÖztürkcan, S; Inan, S; Sahin, MT; Ermertcan, AT; Güzel, EE; Müftüoglu, SHair samples taken from 12-year-old boy prediagnosed with Netherton's syndrome were evaluated by using light and electron microscopic methods. Hair samples were prepared according to routine electron microscopic procedures. Semi-thin sections were stained with methylene blue-azure II, thin sections were contrasted with uranyl acetate-lead citrate. Besides atopy symptoms, hyperparakeratosis and inflammatory cell infiltration were seen in dermis. Results were in accordance with icthyosis linearis circumflexa. In cortex portion of hair, nodulary thickening and swelling were observed. There was a punctured proximal portion like a telescope in distal hair shaft segment. Cells that make up hair cortex were seen to be loosely arranged and there was detachment between cells exterior of cuticle. In evaluating all results trichorrhexis invaginata was identified. Patients given long term therapy for atopic dermatitis, which have breaking of hair in addition to icthyosis, Netherton's syndrome should be thought and investigation of hair samples for supporting the diagnosis is important.Item Changes in epithelial barrier components E-cadherin, Beta-catenin, EGR with steroid treatment in murine model of asthmaYuksel, H; Yilmaz, O; Karaman, M; Firinci, F; Turkeli, A; Kanik, ET; Inan, SItem Effect of PACAP (Pituitary Adenylate Cyclase Activating Polypeptide) and Its Receptor on Oocyte in Vitro MaturationTemel, M; Önal, T; Bilgin, M; Öztatlici, M; Vatansever, SH; Inan, S; Özbilgin, KMItem The distributions of apoptosis and related proteins in ovarian endometriosisVatansever, HS; Inan, S; Giray, G; Sayhan, S; Ozbilgin, K; Sanci, MItem Significance of apoptosis related proteins on malignant transformation of ovarian tumors: A comparison between Bcl-2/Bax ratio and p53 immunoreactivityZeren, T; Inan, S; Vatansever, HS; Sayhan, SIn this study, we compared the immunoreactivities of Bcl-2, Bax and p53 proteins in ovarian tumors and related the immunohistochemical findings to the histological type of the tumors. Formalin-fixed, paraffin wax-embedded tissue sections from 40 patients who had serous-mucinous borderline tumors and serous-mucinous adenocarcinoma of the ovary (n = 10 each) were stained with hematoxylin-eosin (H&E). After histopathological examination, serial sections were stained immunohistochemically with primary antibodies to Bcl-2, Bax and p53 using an avidin-biotin-peroxidase method. A semi-quantitative grading system was used to compare the immunohistochemical staining intensities. The nuclear DNA fragmentation of apoptosis was determined using TUNEL method. As a result of immunohistochemical staining, increased immunoreactivity of Bcl-2 was observed in adenocarcinomas when compared to borderline tumors (P < 0.001). Strong immunoreactivity of Bcl-2 and mild immunoreactivities of Bax and p53 were detected in ovarian adenocarcinomas. There were no significant statistical differences in the immunoreactivity of Bax among the histological type of ovarian tumors. Whereas a balance was observed between the immunoreactivities of Bcl-2 and Bax in the borderline cases, and this balance was strongly changed toward the anti-apoptotic Bcl-2 protein in patients with adenocarcinoma. TUNEL staining of 'sections indicated apoptotic cells in the serous borderline tumors were about 8-fold higher than in the serous adenocarcinoma. The results of this study on apoptosis-related factors might help to develop novel protective and therapeutic approaches, such as isofiavonoids and isothiocyanates, which were associated with decreased Bcl-2/Bax ratio, against the malignant epithelial ovarian tumors. (C) 2014 Elsevier GmbH. All rights reserved.Item Comparison of the effects of extractum cepae, heparin sodium, and allantoin in an experimental model of scar formation: An immunohistochemical and ultrastructural studySahin, MT; Inan, S; Ozturkcan, S; Muftuoglu, SItem A Study on the Anticarcinogenic Effects of Calcium FructoborateTepedelen, BE; Korkmaz, M; Tatlisumak, E; Uluer, ET; Ölmez, E; Degerli, I; Soya, E; Inan, SEvidences about the preventive and therapeutic effects of boron compounds on cancer have been increasing in the last years. Although calcium fructoborate (CaFB) is used as a nutritional supplement, data about its preventive and therapeutic effects on neoplastic transformations are limited. In the present study, the various concentrations of CaFB were applied to the MDA-MB-231 metastatic breast cancer cell line. First, we examined the cytotoxic effect and IC50 value of CaFB by MTT assay. For the evaluation of the DNA damage, apoptosis and metastatic potential, expression levels of ATM, pATM, PARP, p53, p-p53, caspase-3, caspase-9, and VEGF were investigated by using immunoblotting and immunohistochemical methods. Cell viability was significantly reduced at 50 mu M CaFB treatment. pATM, p-p53, and caspase-9 levels increased significantly in all groups; furthermore, there was approximately 12.5-, 2.4-, and 10.7-fold increase, respectively, for 100 mu M CaFB treatment. ATM and p53 levels did not change with CaFB treatment, but PARP levels significantly 2.5-fold decreased. While VEGF immunoreactivity decreased in all groups, significant increase in caspase-3 immunoreactivity was observed only in the group treated with 50 mu M CaFB ( p < 0,001). Our results imply that CaFB may have therapeutic potential as well as preventive benefits in cancer.Item Effects of 5-fluorouracil and gemcitabine on a breast cancer cell line (MCF-7) via the JAK/STAT pathwayUluer, ET; Aydemir, I; Inan, S; Ozbilgin, K; Vatansever, HSAberrant activation of the JAK/STAT pathway may predispose to malignancy as a consequence of the deregulation of cell proliferation, differentiation or apoptosis such as in cancer of the blood, head and neck, and breast. In our study we aimed to investigate the effects of 5-fluorouracil (5-FU) and gemcitabine on a breast cancer cell line (MCF-7 cells) via the JAK/STAT pathway. Distribution of JAK1, JAK2, JAK3 and STAT2, STAT3, STAT4, STAT5 were evaluated on MCF-7 cells following gemcitabine and 5-FU treatment and in the absence of drug treatment by an indirect immunohistochemical method. It was observed that JAK1, JAK3, STAT5 and particularly STAT2 activation were more effective than the other JAK/STATs in breast cancer progression. Following treatment with 5-FU, JAK1 and STAT5 immunoreactivities were decreased in MCF-7 cells in comparison with both gemcitabine-treated and non-treated groups. These results suggest that the JAK/STAT pathway plays an important role in breast cancer pathogenesis and may be more affected after 5-FU treatment rather than gemcitabine. Drugs which block STAT5 may provide a novel therapeutic approach for the treatment of breast cancer. (c) 2011 Elsevier GmbH. All rights reserved.Item Increased vascular surface density in ovarian endometriosisInan, S; Kuscu, NK; Vatansever, S; Ozbilgin, K; Koyuncu, F; Sayhan, SOur goal in this study was to investigate the presence of atigiogenesis-related factors in endometriomas by evaluating their vascular surface densities. Thirty ovarian samples were included in the study. Of these, ten were histologically confirmed endometriomas, ten were ovarian specimens in the follicular phase and ten were ovarian specimens in the luteal phase, serving as controls. Histological specimens were immunostained for von Willebrand factor (vWF: factor VIII-related antigen) and CD34. The area with the highest microvessel density in endometriosis and in the normal ovary was evaluated by using an intercept grid. All microvessels in a specific field (X 100 magnification) were counted and vascular surface density was measured, as 164.01 +/- 21.26 vs. 125.15 +/- 11.28 and 117.44 +/- 9.27 by using vWF, and as 172.97 +/- 25.64 vs. 138.65 +/- 32.21 and 120.34 +/- 18.40 by using CD34 in endometriotic, follicular and luteal ovarian samples, respectively (p < 0.001). The mean vascular surface density was significantly higher in endometriosis than in the ovarian samples of the follicular phase or the luteal phase. No significant difference was seen between normal ovarian samples. Endometriosis was associated with angiogenic properties. Having demonstrated elevated angiogenic factors in endometriotic samples, we concluded that activation of angiogenesis might be a key factor in the pathogenesis of endometriosis.Item Epithelial Barrier Dysfunction and Innate Immune System Interaction in Allergic ResponseYuksel, H; Tayanc, E; Yilmaz, O; Yasar, A; Inan, SItem Significance of tyrosine kinase activity on malign transformation of ovarian tumorsZeren, T; Inan, S; Vatansever, HS; Ekerbicer, N; Sayhan, SEpidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are members of the polypeptide growth factor family. The epidermal growth factor-receptor (EGF-R) is a receptor tyrosine kinase of the ErbB family. Many types of cancer, including ovarian cancer, display enhanced EGF-R immunoreactivity on their cell surface membranes. Also, an increase in TGF-alpha synthesis and secretion usually occurs in human carcinoma cell lines. In this study, we compared the immunoreactivities of TGF-alpha and EGF-R in ovarian tumors and related immunohistochemical findings to the histological type of the tumors. Formalin-fixed, paraffin wax-embedded tissue sections from 40 patients who had serous-mucinous borderline tumor and serous-mucinous adenocarcinoma of the ovary (n = 10 each) were stained with hematoxylin-eosin and labeled for binding of primary antibodies against TGF-alpha and EGF-R using an avidin-biotin-peroxidase method. A semi-quantitative grading system was used to compare immunohistochemical labeling intensities. Increased immunoreactivity of EGF-R and moderate immunoreactivity of TGF-alpha was detected in adenocarcinomas. There was no significant difference in the immunoreactivity of TGF-alpha among the histologic types of ovarian tumors. The results of this study support the hypothesis that EGF-R may be a more useful marker than TGF-alpha in epithelial ovarian tumors. (c) 2007 Elsevier GmbH. All. rights reserved.Item The role of hypoxia related angiogenesis in uterine smooth muscle tumorsUluer, ET; Inan, S; Ozbilgin, K; Karaca, F; Dicle, N; Sanci, MMechanisms of hypoxia-related angiogenesis are important for uterine smooth muscle tumors. Factors that are related to angiogenesis during hypoxia include vascular endothelial growth factor (VEGF), hypoxia inducible factor 1 alpha (HIF1 alpha), T-cell intracellular antigen1 (TIA1), eukaryotic translation initiation factor 2 alpha (eIF2 alpha) and thrombospondin 1 (TSP1). We investigated immunoreactivities of VEGF, HIF1 alpha, TIA1, eIF2 alpha and TSP1 using an indirect immunoperoxidase method for formalin fixed, paraffin embedded tumors that had been diagnosed as leiomyoma (LMY), cellular leiomyoma (CLM) or leiomyosarcoma (LMS). TSP1 immunoreactivity was scored as moderate, mild or minimal, while VEGF, eIF2 alpha and TIA1 immunoreactivities were scored as mild, moderate and strong in LMY, CLM and LMS samples, respectively. HIF1 alpha immunoreactivity was scored as mild to minimal in LMY, CLM and LMS samples, but showed no statistically significant differences among samples. Although angiogenic factors showed strong immunohistochemical staining intensity in LMS, anti-angiogenic factors showed minimal immunohistochemical intensity. There was no difference in HIF-1 alpha immunoreactivity compared to LMY, CLM and LMS samples. We suggest that HIF1 alpha protein synthesis could be suppressed by eIF2 alpha and TIA1. Furthermore, VEGF could be activated by pathways such as COX2, Ras, NF-kappa B or c-myc instead of HIF1 alpha. Angiogenesis could trigger and accelerate tumor development; therefore, anti-angiogenic therapy could be useful for treatment of tumors.Item Significant Changes in Trans-Epithelial Barrier Proteins of Adenoid Tissue with Atopic Status in ChildrenYilmaz, Ö; Simsek, Y; Inan, S; Buga, Ö; Eskiizmir, G; Pinar, E; Kanik, E; Yüksel, HOBJECTIVES: Adenoid tissue is important in local immune response and epithelial barrier dysfunction of this tissue may contribute to allergies. The aim of this study was to evaluate the relationship between the status of cross-epithelial barrier elements in adenoid tissue lymphoepithelium and inhalant allergen sensitization. MATERIALS AND METHODS: Children aged 5-15 years, who underwent adenotonsillectomy, participated in this study. All subjects underwent skin prick testing with environmental inhalant allergens. Occludin, ZO1, e-cadherin, beta-catenin, desmoglein, desmoplakin, and connexon-43 were stained immunohistodiemically in the adenoid tissues obtained and scored by H-score. RESULTS: We enrolled 76 children, 14 among whom were sensitized to environmental allergens. Among the zonula occludens proteins, median H-scores for occludin, claudin, and ZO-1 were significantly lower in the atopic compared to the nonatopic group respectively (p<0.001). Similarly, median H-scores for e-cadherin and beta catenin proteins of the zonula adherens were significantly lower in the atopic group (p<0.001). Both desmoglein and desmoplakin H-scores were significantly lower in the atopic group [60 (50-100) vs 280 (260-300), p<0.001 and 105 (87.5-120) vs 280 (67.25-300), p<0.001 respectively]. Moreover, connexin-43 protein of the gap junction was significantly lower in the atopic group (p<0.001). CONCLUSION: Adenoid tissue, which is the initial point of contact of inhalant allergens demonstrates epithelial barrier junctional protein, changes in children with inhalant allergen sensitization without clinical allergic disease symptoms. Therefore, it may be concluded that epithelial barrier function plays an important role in the development of allergen sensitization versus tolerance.Item DISTRUBUTIONS OF CD44 AND CD24 IMMUNO-REACTIVITY IN HUMAN OVARY CANCERSSanci, M; Ata, N; Inan, S; Dicle, N; Sipahi, CItem Immunolocalization of ERK1/2 and p-AKT in normal endometrium, endometrial hyperplasia, and early and advanced stage endometrioid endometrial adenocancer and their prognostic significance in malignant groupGungorduk, K; Ertas, IE; Sahbaz, A; Ozvural, S; Sarica, Y; Ozdemir, A; Sayhan, S; Gokcu, M; Yilmaz, B; Sanci, M; Inan, S; Harma, M; Yildirim, YObjective: To analyze the expression patterns of extracellular signal-regulated kinase (ERK1/2) and phosphorylated (p)-AKT in the tissues of non-pathologic endometrium, endometrial hyperplasia, and early and advanced stage endometrioid endometrial adenocancer using indirect immunohistochemistry, and also to investigate the effect of ERK1/2 and p-ART expression patterns on prognosis in endometrioid adenocancer. Study design: Immunolocalization of ERK1/2 and p-Ala was examined in six different types of endometrial tissues: proliferative endometrium (PE; n = 10, 11.2%), secretuar endometrium (SE; n = 10, 11.2%), simple hyperplasia (SH; n = 15,16.9%), complex hyperplasia (CH; n=3, 3.4%) and atypical complex hyperplasia (ACH; n = 10, 11.2%), which were obtained from endometrial biopsies, curettage materials, and hysterectomy specimens and classified as the benign group; and both early stage endometrioid (n = 21, 23.6%) and advanced stage endometrioid adenocancer (AC; n=20, 22.5%), which were obtained from complete surgical staging materials and classified as the malignant group. All specimens were fixed in 10% formalin and processed using routine paraffin protocols. Immunostaining intensities were evaluated as negative or weak (assigned as low expression) and moderate or strong (assigned as high expression). Results: In the malignant group, 23 of 41 patients (56.1%) had high ERK1/2 and p-AKT expression, whereas only three of 48 patients in the benign group (6.3%) had high ERK1/2 and p-ART expression (P < 0.0001 and P < 0.0001, respectively), p-ART expression was significantly higher in women with positive lymph nodes (OR 9.0; 95% CI: 1.2-100.0; P = 0.03). Higher expression of p-Ala was significantly associated with poor progression-free survival (PFS) and overall survival (OS). In contrast, ERK1/2 expression was not associated with PFS or OS. Conclusions ERK1/2 and p-ART can be useful in the differential diagnosis of benign vs. malignant endometrial lesions, as well as early vs. advanced stage endometrioid endometrial adenocancer. Additionally, higher p-ART expression could be used as a marker of poor prognosis in the management of patients with endometrioid endometrial adenocancer. (C) 2014 Elsevier Ireland Ltd. All rights reserved.Item The role of CAPE in PI3K/AKT/mTOR activation and oxidative stress on testis torsionDilber, Y; Inan, S; Ercan, GA; Sencan, AIschemia reperfusion injury arises from testicular torsion resulting in a loss of spermatogenesis and significant germ cell apoptosis. This study evaluates the prooxidant/antioxidant effects of caffeic acid phenethyl ester (CAPE) through PI3K/AKT/mTOR signal pathways on testis torsion. A total of (28) male Wistar rats were divided randomly into 4 groups (n = 7 for each group):group A (sham) group,group B torsion/detorsion group, group C (saturation group, during four days of CAPE, one dose (10 mu mol/kg, i.p)) and group D (a single dose of CAPE 2 h after torsion and before detorsion). At the end of the study, unilateral orchiectomies were performed for measurements of MDA and 8OHdG levels, histopathologic and immunohistochemical and TUNEL apoptotic cell examination. Testicular torsion-detorsion led to a significant decrease in the mean values of the Johnsen's scores and a significant increase in the apoptotic cell values of group B. There were no significant differences between group D and group A. In addition, the MDA and 8OHdG levels increased significantly in group B. The MDA and 8OHdG values were lower in group D. However, the 8OHdG levels were higher in group C than the groups A and D. On the other hand, CAPE suppresses mTOR activation and reduces the apoptosis on ischemia/reperfusion damage in rat testis. These results demonstrate that CAPE suppresses mTOR activation and reduces the apoptosis on ischemia/reperfusion damage in rat testis. (C) 2015 Elsevier GmbH. All rights reserved.Item Neural tissue continues its maturation at the site of neural tube closure defectsSelçuki, M; Vatansever, S; Inan, S; Sanci, M; Sayhan, S; Bagdatoglu, CObjective. Our objective was to investigate the relation between the embryological development and neural tissue maturation at the site where the neural plate failed to form a neural tube. Material and methods. Samples from 15 aborted human fetuses with neural tube defects (NTD). All of the fetuses were between 20 and 25 gestational weeks old. Indicators of neural tissue maturation, formation of basal lamina, expression of integrins and neuron specific class III beta tubulin (tuj1) were investigated. To detect the adverse effects of the environment, if any, p53 and bcl-2 activity at both sites of the open and closed neural plate were investigated as well. Results. No difference was found in the expression of maturation-related molecules at the site of the neural plate that remained open compared with the site where the neural tube is normally formed. While high p53 activity was noted in neural tissue at the site of the neural tube defect, no such activity was detected in the neural tissue where the neural tube is normally formed. Conclusion. Our results suggested that maturation and differentiation of neural tissue continued regardless of the failure of neural tube closure. Therefore, the neurological deficits that are encountered in NTD patients should be related to secondary damage such as amnion fluid toxicity, uterus contractions, labor, etc. It seems valuable to save the neural plate before the negative effects of the environment renders the neural tissue functionless.Item Histopathological and ultrastructural effects of Losartan on embryonic rat kidneyAkil, I; Inan, S; Gurcu, B; Nazikoglu, A; Ozbilgin, K; Muftuoglu, SThe aim of our study was to investigate the histopathological, immunohistochemical and ultrastructural effects of Losartan (a selective angiotensin II type-1 receptor blocker) on renal development in rats. Twelve pregnant rats were divided into control and experimental groups. In the experimental group, Losartan (10mg/kg/day) was given via nasogastric tube, between the sixth day of implantation and time of sacrifice on embryonic days 18 and 20. All formalin-fixed, paraffin wax-embedded renal tissue sections were stained with hematoxylin and eosin or labelled for binding of primary antibodies against transforming growth factor-it (TGF-beta 1,-2,-3) using an avidin-biotin-peroxidase method. For electron microscopic examination, samples were fixed with glutaraldehyde and osmium tetroxide and embedded in araldite. Glomerular basement membrane (GBM) thickness was measured and compared using an unpaired t-test. Angiotensin II type-1 receptor antagonism by Losartan inhibited renal growth and delayed nephron maturation. Increased immunoreactivity of TGF-beta's was observed in developing nephron precursors and interstitial cells in the experimental group. Electron microscopical examination showed that thickening of the GBM was normal in the control group but an irregular thickening was seen in the experimental group (p < 0.001). It was also seen that epithelial cells of developing tubules underwent apoptosis in the experimental group. Thus, renal development in rats seems to depend on an intact renin-angiotensin system. (c) 2005 Elsevier GmbH. All rights reserved.